Title: Maintenance of cone photoreceptor outer segments Abstract: Cone photoreceptors are essential for perception of color and for high-acuity vision. In industrialized countries, we rely more on cone mediated vision than on rod mediated vision, both during the day and during most of the night. Degeneration of cones is causative to a number of blinding disorders, including macular degeneration, retinitis pigmentosa, and cone dystrophy. Etiology of those blinding disorders is often associated with deficiencies in the maintenance of the photoreceptive outer segment (OS). The process of OS morphogenesis is poorly understood in cones. We have developed a new method to fluorescently label newly synthesized proteins and track their movements via fluorescence microscopy in live Xenopus laevis cones. By using this method, we will study the mechanism of cone OS protein renewal. Cone OSs contain open disks (also called lamellae) that are interconnected and continuous with the plasma membrane. We will clarify whether diffusion barrier exist between open disks and gain insight into the redistribution of membrane proteins after their delivery to the cone OSs. Such studies are critical for the understanding of how cone OS membrane proteins are renewed. Impaired maintenance of cone OS is observed in a broad spectrum of blinding disorders such as Bardet Biedl Syndrome, Usher Syndrome, and other non-syndromic forms of retinitis pigmentosa. This study could reveal novel pathways that would be harnessed to treat these blinding disorders.